Sparing the hippocampus during prophylactic cranial irradiation (PCI) better preserved cognitive function without increasing brain metastasis in patients with small-cell lung cancer (SCLC), according to a phase 3 study published in the Journal of Clinical Oncology.

The study authors noted that whole-brain radiotherapy has been associated with neurocognitive decline due to radiation-induced hippocampal injury. However, a “key concern” of using hippocampal avoidance (HA) PCI in patients with SCLC is the potential risk of brain metastasis within the HA zone.

In a phase 3 trial (ClinicalTrials.gov Identifier: NCT02397733), researchers examined the neurotoxicity of PCI and evaluated the benefits and risks of sparing the hippocampus in patients with SCLC. 


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The study enrolled 150 patients. They were randomly assigned 1:1 to receive PCI or HA-PCI. The median follow-up was 40.4 months for surviving patients and 21.0 months for all randomly assigned patients.

The primary endpoint for comparing PCI with and without HA was the delayed free recall score, assessed at 3 months after treatment completion using the Free and Cued Selective Reminding Test (FCSRT). Secondary endpoints included other FCSRT outcome measures, brain metastasis, adverse events, quality of life, and overall survival (OS).

The proportion of patients with a decline in delayed free recall at 3 months was significantly lower in the HA-PCI arm than in the PCI arm — 5.8% and 23.5%, respectively (odds ratio [OR], 5.0; 95% CI, 1.57-15.86; P =.003). 

The proportion of patients with a decline in total recall from baseline to 3 months was significantly lower in the HA-PCI arm than in the PCI arm as well — 8.7% and 20.6%, respectively (OR, 2.7; 95% CI, 0.97-7.57; P =.049). 

However, there was no significant difference between the arms for total free recall (P =.16) or delayed total recall (P =.074) from baseline to 3 months.

At 6 months, patients in the PCI arm had a significantly greater decline in total recall (P =.035), total free recall (P =.040), and delayed free recall (P =.005) but not delayed total recall (P =.06). 

At 12 months, there were no significant differences between the treatment arms for any neurocognitive function endpoints. However, at 24 months, patients in the PCI arm had a significantly greater decline in total recall (P =.019).

The researchers found no significant difference in the incidence of brain metastasis between the treatment arms. At 2 years, the cumulative incidence of brain metastasis was 22.8% in the HA-PCI arm and 17.7% in the PCI arm (P =.430).

Furthermore, there was no significant difference in OS between the treatment arms. The median OS was 23.4 months for the HA-PCI arm and 24.9 months for the PCI arm (P =.556).

Finally, there were no significant differences between the arms in quality of life or toxicity. Most patients were asymptomatic, and no toxicities greater than grade 2 were reported.

“This study is an important step introducing a new therapeutic approach to patients with SCLC [who are] candidates for PCI,” the study authors wrote. “On the basis of the results of this study, we conclude that hippocampal avoidance-PCI should be considered standard of care for patients with SCLC who plan to receive PCI.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference 

Rodrıguez de Dios N, Couñago F, Murcia-Mejia M, et al. Randomized phase III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small-cell lung cancer (PREMER): A GICOR-GOECP-SEOR study. J Clin Oncol. Published online August 11, 2021. doi:10.1200/JCO.21.00639

This article originally appeared on Cancer Therapy Advisor